Patent application title: Apparatus and process for encapsulating capsules or other solid dosage forms within capsules

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Abstract:

The present invention provides an apparatus and process for making
softgel capsules having incorporated therein other solid dosage forms
selected from the group consisting of pellets, smaller capsules, smaller
tablets, sustained release solid dosage forms, immediate release solid
dosage forms, extended release solid dosage forms and zero order release
solid dosage forms, said apparatus comprising: (a) two spreader boxes;
(b) two casting drums; (c) a pair of rotary dies having means for
suction; (d) a liquid fill system; (e) a wedge for heating gelatine
ribbons and feeding said fill; and (f) two lateral dispensing devices
said lateral dispensing devices including hoppers having said solid
dosage forms, channelguides for transporting said solid dosage forms and
a grasping claw for dispensing said solid dosage form into the softgel
pocket formed in the rotary dies.

Claims:

1. An apparatus for making softgel capsules having incorporated therein
other solid dosage forms selected from the group consisting of pellets,
smaller capsules, smaller tablets, sustained release solid dosage forms,
immediate release solid dosage forms, extended release solid dosage forms
and zero order release solid dosage forms, said apparatus comprising: (a)
two spreader boxes; (b) two casting drums; (c) a pair of rotary dies
having means for suction; (d) a liquid fill system; (e) a wedge for
heating gelatine ribbons and feeding said fill; and (f) two lateral
dispensing devices said lateral dispensing devices including hoppers
having said solid dosage forms, channelguides for transporting said solid
dosage forms and a grasping claw for dispensing said solid dosage form
into the softgel pocket formed in the rotary dies.

2. A dispensing device for dispensing and feeding solid dosage forms into
a softgel capsule said dispensing and feeding device including a hopper
having said solid dosage forms, channelguides for transporting said solid
dosage forms and a grasping claw for dispensing said solid dosage form.

3. A method for making softgel capsules having incorporated therein other
solid dosage forms, said method comprising: (a) casting a gel forming
composition to make films; (b) passing said films through a pair of
rotary dies having vacuum means to make pockets; (c) feeding smaller
solid dosage forms into said pockets using a lateral dispensing and
feeding system that uses a grasping claw; (d) filling said pockets with a
medicine formulation in liquid form via a wedge segment; and (e) forming
said capsule by sealing the pockets together.

4. A process for making a softgel capsule having incorporated therein
another capsule, said method comprising: (a) feeding film sheets between
a first die roll and a second die roll wherein each of the die rolls have
capsule pockets in a plurality of rows and said capsule pockets have at
least one orifice for application of suction; (b) applying suction while
said film is in place in the capsule pockets; (c) feeding via
guidechannels through a lateral dispensing device having a hopper and a
grasping claw preformed smaller capsules onto the film sheets overlying
the die rolls at positions having the capsule pockets; (d) filling said
capsule pockets also via a wedge segment with a liquid medical
formulation; and (e) cutting the film sheets about the capsule pockets to
form said soft gel capsules having capsules in combination with a
suitable liquid pharmaceutical combination.

5. A softgel capsule having incorporated therein another solid dosage
form selected from the group consisting: (a) one capsule contains an
omega oil and the other solid dosage form is a capsule having a statin;
(b) once capsule contains a non-steroidal antiinflammatory and the other
solid dosage form contains and antihistamine; and (c) one capsule
contains and omega oil and the other solid dosage form contains a
salicylate.

6. The softgel capsule of claim 5 wherein said omega oil is an omega-3
oil and the statin is selected from the group consisting of mevastatin,
lovastatin, pravastatin, fluvastatin, simvastatin, rosuvastatin,
cerivastatin and atorvastatin and derivatives and analogs thereof.

8. The softgel capsule of claim 5 wherein said salicylate is
acetylsalicylic acid.

Description:

[0001] This application claims the priority benefit under 35 U.S.C.
section 119 of U.S. Provisional Patent Application No. 61/344,416
entitled "Apparatus And Process For Encapsulating Capsules Within
Capsules" filed Jul. 19, 2010, which is in its entirety herein
incorporated by reference.

FIELD OF THE INVENTION

[0002] This invention relates to methods and apparatus for the production
of soft gelatin capsules containing internally other solid dosage forms
or smaller capsules within said capsules. The capsules of the invention
are now well established as a means for providing a variety of liquid
products such as drugs and dietary supplements in a readily ingestible
form especially when two drugs are not compatible with each other.

[0003] This invention further relates to softgels (or soft gelatin
capsules) containing one or more smaller capsules within such capsules
and to a process and apparatus for the manufacture thereof. The present
invention also relates to a gelatin capsule of the soft type containing
multiple active ingredients or the like, and more particularly to a novel
gelatin capsule capable of containing multiple medicines or dietary
supplement as the content separated from each other, and its
manufacturing method and manufacturing apparatus.

[0004] The present invention also relates generally to a method and
apparatus for forming capsules within capsules containing a measured
amount of not compatible medicinals and more particularly to a method and
apparatus for forming capsules. The method and apparatus of the present
invention are particularly useful in connection with forming softgel
capsules having other solid dosage forms containing multiple
pharmaceutical product, such as for example medicines, vitamins, food
supplements and the like which are not compatible with each other.

[0005] The present invention further relates to encapsulation machines
and, more particularly, to soft encapsulation machines which make soft
gelatin capsules having other smaller capsules within or other solid
dosage form.

[0006] The invention is particularly useful for making formulations
wherein two active ingredients are not compatible with each other but it
is desirable to administer them in the same dosage form i.e., a capsule
within a capsule or another solid dosage form within a capsule.

BACKGROUND OF THE INVENTION AND DESCRIPTION OF THE PRIOR ART

[0007] The art of encapsulation bas been known for many years,
particularly for the production of unit dosage forms containing various
pharmaceutical products. Normally, such pharmaceutical capsules are
composed of gelatin or some modification thereof, which is fabricated
essentially into two different forms, namely, the so-called hard gelatin
capsule and the soft gelatin capsule.

[0008] It is also known that conventional soft gelatin capsules are a
preferred from of administration for medicaments and similar products;
especially liquids, pastes, solids dispersed in liquids, or dry solids.
Soft gelatin capsules also possess particular advantages for substances
which require total protection from air and light, because the gelatin is
completely sealed around the contents. An important example is for the
encapsulation of vitamins, which has resulted in a high degree of
stability thereof.

[0009] Hard gelatin capsules are also known in the art, and are generally
formed from two distinct parts, namely the "cap" and the "body", fitting
one into the other so as to form the complete capsule. The cap and the
body are manufactured by the same process consisting of immersing in a
gelatin solution the end of a mandrel whose form corresponds to the inner
volume of the cap or of the body, then withdrawing the mandrel from the
solution and letting the layer of gelatin thus deposited dry, which is
then removed like a glove finger. Hard shell capsules so formed have
problems of leakage and do not provide adequate protection from air and
light

[0010] Soft gelatin capsules, now more commonly known as softgels, have
been well known and widely used for many years. Softgels generally
comprise an outer shell primarily made of gelatin, a plasticizer, and
water, and a fill contained within the shell. The fill may be selected
from any of a wide variety of substances that are compatible with the
gelatin shell. Softgels are widely used in the pharmaceutical industry as
an oral dosage form containing many different types of pharmaceutical and
vitamin products. In addition to use as an oral dosage form for drugs and
vitamins, soft gelatin capsules or softgels are also designed for use as
suppositories for rectal or vaginal use. Other uses are for topical and
ophthalmic preparations and the like. The cosmetic industry also uses
softgels as a specialized package for various types of perfumes, oils,
shampoos, skin creams and the like. Softgels are available in a great
variety of sizes and shapes, including round shapes, oval shapes, oblong
shapes, tube shapes and other special types of shapes such as stars. The
finished capsules or softgels can be made in a variety of colors. Also,
opacifiers may be added to the shell.

[0011] The process for making softgel capsules includes the step wherein
the gelatin shell and the fill material come together to form Softgel
capsules. It takes place in a closed environment called clean room where
the relative humidity is around 20%. The gelatin shell and fill material
are brought together simultaneously in the encapsulation machine.

[0012] The process is basically performed as follows: a pump delivers the
warm gelatin over two chilled drums which are located at both opposite
sides of the machine, through a spreader box that sits over each drum.
The warm liquid gelatin flows over the drums and this transforms the
liquid gelatin into two solid ribbons of gel. The left and right ribbons
pass over rollers which feed them through two die rolls. These die rolls
determine the shape and size of softgels and cut the Softgel shell from
the ribbons as they turn around.

[0013] Simultaneously, a sensitive and high accuracy positive displacement
pump delivers the fill material into a heated wedge which sits between
rotary dies. This wedge injects the fill material into the die cavities
between ribbons just right before the die rolls cut the ribbons and seal
the two halves together. Warm just formed softgels slide gently through a
chute onto a conveyor belt which carries them to the tumble dryer where
cooling and drying process takes place.

[0014] In more specific detail, typical soft encapsulation machines form
at least two flexible gelatin sheets or ribbons by cooling molten gelatin
on separate drums then lubricating and guiding the sheets into
communication with each other over co-acting dies while simultaneously
dispensing a desired quantity of fill material between the sheets in
synch with cavities in the outer surfaces of the dies to produce soft
capsules. The encapsulation machines typically utilize gearing to control
the relative rotations of the various components and fill mechanisms to
synchronize the operation of these various components. The
synchronization of these various components, however, can vary depending
upon a variety of factors, such as the particular dies used, the number
of cavities and the size of the cavities on the dies, and the type of
material used to form the sheets. To change the synchronization of the
various components, mechanical gears are required to be changed to obtain
the desired ratios and synchronization of these components. The changing
of gears, however, is time intensive. Additionally, the use of mechanical
gears provides finite gear ratios which limit the synchronization of the
various components to the mechanical gears that are available. Thus, it
would be advantageous to provide a capsule machine wherein the
synchronization and rates at which the various components operate can be
altered without the necessity of changing gears. Additionally, it would
be advantageous if the synchronization between the various components can
be infinite to thereby allow more precise synchronization between the
various components. It would also be advantageous to allow various
components, such as the fill mechanism, to be adjusted independently of
the other components while the machine is running to allow for
adjustments of the timing of fill material inserted into each of the soft
capsules. It would also be advantageous to eliminate the use of casting
drums in the making of softgel capsules.

[0015] During the operation of the capsule making machine, the contact
between the adjacent dies can be adjusted by the operator of the capsule
making machine. Typically, the operator is able to move one of the dies
closer to the other die so that the pressure or force exerted on the
sheets passing between the adjacent dies can be adjusted. Such
adjustments, typically are mechanical adjustments made by fluid
actuators, such as pneumatic cylinders. The operator is able to adjust
the pneumatic pressure thereby altering the force the dies exert on one
another and on the sheets. This adjustability allows an operator to
customize the pressure to ensure that quality soft capsules are produced.
However, the dies are susceptible to premature failure and/or wear when
the pressure or force between the two dies is more than that required to
produce acceptable soft capsules. Thus, it would be advantageous to
monitor/record the pressure applied to the dies so that quality capsules
are produced without inducing excessive wear or premature wear on the
dies.

[0016] A material fill mechanism is used to supply the fill material that
is encapsulated within the soft capsules. When the fill material is a
liquid, such as a liquid medication or die for a paint ball capsule, the
fill mechanism includes a plurality of positive displacement plunger-type
pumps that are arranged in a housing above the dies. The plunger-type
pumps are positioned on a yoke that moves linearly in a reciprocating
motion to allow the plunger-type pump to fill with the liquid fill
material on one stroke and subsequently discharge the liquid fill
material on the other stroke. A valving arrangement between opposing
pumps is utilized to control the discharge and filling of the pumps. The
valve arrangement includes a sliding member that moves linearly back and
forth in a direction generally perpendicular to the linear motion of the
yoke. The discharge of the liquid fill material into the sheets as they
are passing through the dies is coordinated with the operation of the
dies to insure that the timing of the injection of the liquid fill
material is synchronized with the cavities on the dies. Typically, this
synchronization has been performed through the use of mechanical gears
that link the timing of the stroke to the rotation of the dies. Thus, in
order to adjust the synchronization a mechanical gear change is required
which is time consuming. Additionally, the timing is limited to a finite
number of gear ratios as determined by the gears that are available.

[0017] The sliding member of the valving mechanism requires lubrication.
Typically, the lubrication is provided by a lubricating pump with its own
separate drive. However, the use of a separate drive to operate the
lubricating pump adds additional complexity and components to the capsule
machine. Thus, it would be advantageous if a motion of the slide member
and/or the yoke could be utilized to drive the lubrication pump.

[0018] The pumps are typically contained within a housing that is filled
with a lubricating oil that is used to lubricate the sliding member. The
pumps, however, can leak around their seals and contaminate the
lubricating oil with the leaking fill material. Contamination of the oil
requires a time consuming and possibly difficult clean up and can cause
the lubricating oil to not perform as designed thereby increasing the
wear on the sliding surfaces and decreasing the life span of the sliding
surfaces. Thus, it would be advantageous to capture any fill material
that leaks from the pumps and deter or prevent the liquid fill material
from contaminating the lubricating oil within the pump housing.

[0019] The pumps are typically driven by a drive mechanism that is also
located within the pump housing. Because the drive mechanism is located
in the pump housing, it is possible for liquid fill material that leaks
from the pumps to contaminate not only the lubrication oil but also the
drive mechanism. When switching from one fill material to another, the
pump and all of the components in the pump housing are required to be
thoroughly cleaned to remove all contamination. The locating of the drive
mechanism within the pump housing provides additional components that
must also be cleaned when changing the fill material. Thus, it would be
advantageous to separate the drive mechanism from the pump housing to
reduce the components that are required to be cleaned when changing fill
material.

[0020] The soft capsules produced by the encapsulation machine are
transported from the encapsulation machine to a dryer to additionally dry
the soft capsules and to make them into final form. The soft capsules are
transported from the encapsulation machine to the dryer by a conveyor
that extends along the front of the encapsulation machine. The conveyor
can be contaminated by the fill material during operation of the
encapsulation machine. When it is desired to switch the product being
produced on the encapsulation machine, the conveyor must be removed from
the encapsulation machine and cleaned to remove any contaminates thereon.
The conveyor is driven by a motor that is attached to the conveyor. When
it is necessary to remove the conveyor for cleaning, the motor must also
be taken with the conveyor which makes it more difficult to remove and
transport the conveyor and requires additional time to disconnect the
motor from the encapsulation machine. The present invention provides an
encapsulation machine that overcomes the above-described disadvantages of
typical encapsulation machines.

[0021] Applicant is aware of the following publications briefly discussed
below. U.S. Pat. No. 1,970,396 features a method and machine for
producing soft gelatin capsules in an automated process. The method
involves the formation of two gelatin sheets or films through the use of
a gravity fed spreader box, cooling the liquid gelatin on two separate
webs, then lubricating and guiding the two sheets into communication with
each other between two co-acting dies while simultaneously dispensing the
proper amount of medicine or other filling material between the sheets in
registration with half cavities in the outer surface of the dies.

[0022] U.S. Pat. No. 5,761,886 discloses an apparatus for forming capsules
that provides rotary dies that are independently moveable and the ability
to vary the speed of the dies during the formation of a single capsule.
The '886 device also utilizes independently controlled casting drums to
reduce "set-up" time and provide better quality control. Even though the
'886 patent discloses a very sophisticated encapsulation machine, it
still utilizes a gravity fed spreader box for formation of the
encapsulating ribbon.

[0023] Other patents relating to encapsulation techniques which disclose
the use of spreader boxes to create the film or ribbon on a casting drum
include U.S. Pat. Nos. 2,288,327; 2,774,988; 5,246,638; 5,735,105; and
6,022,499.

BRIEF DESCRIPTION OF THE DRAWINGS

[0024] FIG. 1 is a front view of the complete apparatus of the invention
showing all the elements of the apparatus.

[0025]FIG. 2 is also a front view of the apparatus of FIG. 1 without the
spreader boxes and casting drums.

[0026]FIG. 3 is a front view of the mechanism for filling the capsules
with other capsules.

[0027]FIG. 4 is also a front view of how the smaller capsules are
dispensed into the larger capsule.

[0028]FIG. 5 shows the smaller capsule hopper having capsules which are
fed via guiding channels into the larger capsule.

[0029]FIG. 6 shows a representative end product of the invention
containing two capsules inside another capsule.

[0030]FIG. 7 are representative examples of products contemplated by the
invention.

SUMMARY OF THE INVENTION

[0031] The present invention responds specifically to the long-felt need
heretofore unmet by the prior art, and especially with a view to
overcoming the inherent inadequacies of combination of pharmaceuticals
that are not compatible for oral delivery to mammals. The composition is
a pharmaceutical combination i.e., a capsule within a capsule providing
the convenience and reliability of oral administration, while providing
near simultaneous delivery in vivo of incompatible substances. The
composition is shelf stable when formulated.

[0032] The foregoing, and other advantages of the present invention, are
realized in one aspect thereof in an oral pharmaceutical composition that
is a combination of incompatible active ingredients. The composition
comprises a double soft capsule which includes one pharmaceutical in a
first capsule which is enclosed second soft capsule also containing a
second active ingredient. The soft capsules are preferably made of
gelatin. The active ingredients may be combined with acceptable grade
carriers.

[0033] In another aspect, the invention is a method of simultaneously
delivering incompatible compounds to mammals in vivo. Such delivery is
achieved by administering orally to a mammal a double soft capsule
containing a first substance in a first capsule, which is enclosed with a
second substance, incompatible with the first substance, in a second
larger soft capsule. In another embodiment, this invention provides a
method for preparing shelf-stable compositions of incompatible
substances, which includes the use of multiple capsules of variable
composition. Such method is accomplished manually or by the apparatus of
the invention further described below.

[0034] As used herein, the term "incompatible" is meant to refer to
substances which deleteriously react with one another when combined in
desired levels or concentrations.

[0035] The invention also provides an apparatus for making softgel
capsules having incorporated therein other solid dosage forms selected
from the group consisting of pellets, smaller capsules, smaller tablets,
sustained release solid dosage forms, immediate release solid dosage
forms, extended release solid dosage forms and zero order release solid
dosage forms, said apparatus comprising: (a) two spreader boxes; (b) two
casting drums; (c) a pair of rotary dies having means for suction; (d) a
liquid fill system; (e) a wedge for heating gelatine ribbons and feeding
said fill; and (f) two lateral dispensing devices said lateral dispensing
devices including hoppers having said solid dosage forms, channelguides
for transporting said solid dosage forms and a grasping claw for
dispensing said solid dosage form into the softgel pocket formed in the
rotary dies.

[0036] The invention further provides a dispensing device for dispensing
and feeding solid dosage forms into a softgel capsule said dispensing and
feeding device including a hopper having said solid dosage forms,
channelguides for transporting said solid dosage forms and a grasping
claw for dispensing said solid dosage form.

[0037] The instant invention also provides a method for making softgel
capsules having incorporated therein other solid dosage forms, said
method comprising: casting a gel forming composition to make films; (b)
passing said films through a pair of rotary dies having vacuum means to
make pockets; (c) feeding smaller solid dosage forms into said pockets
using a lateral dispensing and feeding system that uses a grasping claw;
(d) filling said pockets with a medicine formulation in liquid form via a
wedge segment; and (e) forming said capsule by sealing the pockets
together.

[0038] The invention is also a process for making a softgel capsule having
incorporated therein another capsule, said process comprising: (a)
feeding film sheets between a first die roll and a second die roll
wherein each of the die rolls have capsule pockets in a plurality of rows
and said capsule pockets have at least one orifice for application of
suction; (b) applying suction while said film is in place in the capsule
pockets; (c) feeding via guidechannels through a lateral dispensing
device having a hopper and a grasping claw preformed smaller capsules
onto the film sheets overlying the die rolls at positions having the
capsule pockets; (d) filling said capsule pockets also via a wedge
segment with a liquid medical formulation; and (e) cutting the film
sheets about the capsule pockets to form said soft gel capsules having
capsules in combination with a suitable liquid pharmaceutical
combination.

[0039] The invention further provides softgel capsules incorporated into
an outer softgel capsule, tablets incorporated into an outer softgel
capsule, microgranules incorporated into an outer softgel capsule, and
any combination between softgels, tablets and/or microgranules
incorporated into an outer softgel capsule.

[0040] The instant invention also provides a softgel capsule having
incorporated therein another solid dosage form selected from the group
consisting: (a) one capsule contains an omega oil and the other solid
dosage form is a capsule having a statin; (b) one capsule contains a
non-steroidal antiinflammatory and the other solid dosage form contains
and antihistamine; and (c) one capsule contains and omega oil and the
other solid dosage form contains a salicylate.

[0041] Other advantages and a fuller appreciation of the specific
adaptations, compositional variations, and physical and chemical
attributes of the present invention will be gained upon an examination of
the following detailed description of the invention, taken in conjunction
with the accompanying drawings and appended claims.

DETAILED DESCRIPTION OF THE INVENTION

[0042] The present invention provides an innovative and efficient system
for the manufacture of capsules with two or more internal components.
Although the internal components may be incompatible the invention is
also intended to provide internal components that are compatible but are
intended to be released at different intervals.

[0043] The present invention provides an advanced drug delivery system
that places different pharmaceuticals forms in a single dosage
combination. The invention allows delivering incompatible pharmaceutical
actives in the form of solid, liquid, microgranules, gels, hard shell or
soft gel capsules within an outer softgel capsule.

[0044] The novel dosage system allows for combining different therapeutic
entities that have never been combined before, via oral, ovules, or
suppositories.

[0045] For the multi-drugs regimen patients and due to the incompatibility
of some actives that can not be combined in a single dose, the instant
invention offers a universe of possibilities for current and future new
drugs combinations and supplies different releasing delivery.

[0046] In the present invention, existing and proven delivery systems are
combined in a highly reliable, easy to use and affordable manufacture
that give the resulting dosage form unique characteristics to deliver
single or multiple APIs regardless of physical-chemical compatibility
and/or stability liabilities.

[0047] For the multi-drugs regimen patients this delivery system is a
viable alternative; due to the manufacturing of IR plus MR combinations
in tablets and hard-gelatin capsules while enhancing dosing accuracy and
by-passing dissolution barriers and coating issues. It allows the
formulation of combination products, highly needed to assure patient
compliance and allow synergic clinical effects in a safe and stable
dosage form.

[0048] Some of the most important advantages are:

Fast and sustained release in a single dose. Gastric or intestinal
release in the same dose. Fewer intakes to be administered. Simplicity of
regimen reduces mistakes. Impossible to be falsified. Reduces number of
Rx's prescribed by Physician. Smaller number of presentations to
maintain.

[0049] The invention further provides soft-gelatin capsules as a
immediate-release (IR) delivery system, that upon rupture, it releases
immediate or modified release (MR) tablets, capsules, softgels, granules
and/or microgranules. Compatible and/or incompatible pharmaceutical
active ingredients, and/or blends of IR and MR dosage forms of the same
or different active pharmaceutical ingredients (APIs) can be dosed
simultaneously in a single capsule. These capsules may be designed to be
administered orally, vaginally or rectally, as needed.

[0050] Referring in detail to the apparatus shown in FIG. 1, reference
numeral 1 illustrates a medicine hopper having a cover 2 and a medicine
feeder 3 connected with a clamp. The apparatus further includes a
medicine distributor system 4, pump 5 to pump medicine and further
includes plunger 6. The apparatus also includes a fitting distributor
connection 7, medicine tubing/hoses 8, a segment coupling connection 9, a
support segment 10, and wedge segment 11.

[0051] The apparatus has lateral hoppers 12 and 13 containing smaller
capsules or other solid dosage forms that are intended to be encapsulated
by the soft gels being formed in the rotary dies. The lateral hopper
dispensing system includes acrylic or other material knob fasteners 14
and acrylic substrate 15 having guide channels/tracks 16 for the smaller
capsules or other smaller solid dosage forms such pellets or minitablets,
etc. The lateral dispensing system of the invention includes a grasping
claw 17 for dispensing the smaller capsules coming through channels/track
16. The apparatus further includes the conventional aspects of making
softgel capsules which includes a gelatin film 18, guiding rollers 19,
tensioner 20, rotary mold 21, a vacuum system 22, capsule exit 23 after
the capsule is formed, a yoke support arm 24, housing 25, spreader gel
dispensing boxes and casting drum 27.

[0052]FIG. 2 illustrates the apparatus of FIG. 1 without the spreader gel
dispensing boxes and casting drums. The reference numerals in FIG. 2 are
identical as those in FIG. 1.

[0053] The film-forming materials of the invention comprise at least one
component selected from the group consisting of gelatin, starch,
carrageenans, gums or synthetic materials such as
hydroxypropyl-methylcellulose (HPMC), other hydroxyalkylated celluloses
and the like. The film-forming material typically has an aqueous base and
is considered to be ingestible. As used herein, the term "ingestible" is
used to indicate a film-forming material that dissolves under conditions
simulating the human digestion tract or water.

[0054]FIG. 3 shows the dispensing and feeding of solid dosage forms or
capsules that come from hoppers 12 and 13 (not shown--See FIGS. 1 and 2)
controlled by grasping claw 17 with volume capacity for accurate dosing
fixed within the capsule. The smaller dosage form or smaller capsules is
fed through guide channels 16 and deposited inside a half pocket as the
softgel capsule is being formed in rotary die 21. The grasping claw 17
releases each capsule into each packet as the rotary die moves. The final
capsule is also filled with additional pharmaceutical actives in liquid
form injection tubing 8. After filling the formed capsule 23
falls-through to a conveyor belt and then transported for drying.

[0055]FIG. 4 further illustrates in more details the feeding of solid
dosage forms or capsules into the rotary molding process for making
softgel capsules containing internally other dosage forms such as smaller
capsules, pellets, small tablets, etc. The feeding of the internal
capsule is made by an independent dispenser having guide channels 16 so
that as capsules are deposited in the pocket of the rotary die/mold 21,
the wedge segment 11 is used to simultaneously dispense a liquid medicine
product to fill the capsule. As is well known gelatin film 18 is used to
form the softgel pocket in the rotary die/mold 21.

[0056]FIG. 5 shows one of the lateral hoppers having smaller solid dosage
forms or smaller capsules to be filled inside another softgel capsule.
The hopper 12 having capsules 13, are released from the hopper and
deposited and guided through guidechannels 16 which in turn leads to the
pocket in the rotary mold that is in a tangential position.

[0057]FIG. 6 illustrates a finished capsule of the invention. One or more
smaller capsules may be encapsulated in any way into another immersed in
a liquid or solution containing a pharmaceutical active ingredient.

[0058] The resulting products of the invention include softgel capsules
having incorporated therein another solid dosage form selected from the
group consisting: (a) one capsule contains an omega oil and the other
solid dosage form is a capsule having a statin; (b) one capsule contains
a non-steroidal antiinflammatory and the other solid dosage form contains
and antihistamine; and (c) one capsule contains and omega oil and the
other solid dosage form contains a salicylate.

[0059] Typically the omega oil is an omega-3 oil and the statin is
selected from the group consisting of mevastatin, lovastatin,
pravastatin, fluvastatin, simvastatin, rosuvastatin, cerivastatin and
atorvastatin and derivatives and analogs thereof.

[0061] The antihistamine is selected from the group consisting of:
diphenhydramine, loratadine, cetirizine, fexofenadine, hydroxyzine,
cyproheptadine, chlorphenamine, clemastine and desloratadine.

[0062] The salicylate is typically acetylsalicylic acid.

[0063] The present invention provides delivery systems which are combined
in a highly reliable, easy to use and affordable manufacture that give
the resulting dosage form unique characteristics to deliver single or
multiple APIs regardless of physical-chemical compatibility and/or
stability liabilities. The soft-gelatin delivery system can be filled
with hydrophilic or lipophilic media to suspend various IR and/or MR
dosage forms in drug solutions or plain liquid phases.

[0064] The delivery system of the invention is a viable alternative to the
manufacturing of IR plus MR combinations in tablets and hard-gelatin
capsules while enhancing dosing accuracy and by-passing dissolution
barriers and coating issues. It also solves compatibility and stability
issues for multivitamins, cold remedies, nutraceuticals and multiple
other OTC medications. The invention also allows the formulation of
combination products, highly needed to assure patient compliance and
allow synergistic clinical effects in a safe and stable dosage form.

[0065] The invention also allows for ease of identification by color
coding the shell, fill and/or contents minimizing counterfeiting risks.

[0066] The contents of my copending non-provisional applications filed
Jul. 18, 2011, and concurrently filed with this application and based on
provisional applications No. 61/344,417 and 61/344,416 are incorporated
by reference in their entirety as if they were individually denoted.

[0067] All patents, patent applications and publications cited in this
application including all cited references in those applications and
publications, are hereby incorporated by reference in their entirety for
all purposes to the same extent as if each individual patent, patent
application or publication were so individually denoted.

[0068] While the many embodiments of the invention have been disclosed
above and include presently preferred embodiments, many other embodiments
and variations are possible within the scope of the present disclosure
and in the appended claims that follow. Accordingly, the details of the
preferred embodiments and examples provided are not to be construed as
limiting. It is to be understood that the terms used herein are merely
descriptive rather than limiting and that various changes, numerous
equivalents may be made without departing from the spirit or scope of the
claimed invention.